tbuckley/cabot-search huggingface dataset:
The alarmin interleukin-33 promotes the expansion and preserves the stemness of Tcf-1+ CD8+ T cells in chronic viral infection
Authors: Anna-Friederike Marx, Sandra M. Kallert, Tobias M. Brunner, José A. Villegas, Florian Geier, Jonas Fixemer, Tiago Abreu-Mota, Peter Reuther, Weldy V. Bonilla, Jelizaveta Fadejeva, Mario Kreutzfeldt, Ingrid Wagner, Patricia Aparicio-Domingo, Leo Scarpellino, Mélanie Charmoy, Daniel T. Utzschneider, Claudia Hagedorn, Min Lu, Karen Cornille, Karsten Stauffer, Florian Kreppel, Doron Merkler, Dietmar Zehn, Werner Held, Sanjiv A. Luther, Max Löhning, Daniel D. Pinschewer
Journal: Immunity (2023)

T cell factor 1 (Tcf-1) expressing CD8+ T cells exhibit stem-like self-renewing capacity, rendering them key for immune defense against chronic viral infection and cancer. Yet, the signals that promote the formation and maintenance of these stem-like CD8+ T cells (CD8+SL) remain poorly defined.Studying CD8+ T cell differentiation in mice with chronic viral infection, we identified the alarmin interleukin-33 (IL-33) as pivotal for the expansion and stem-like functioning of CD8+SL as well as for virus control. IL-33 receptor (ST2)-deficient CD8+ T cells exhibited biased end differentiation and premature loss of Tcf-1. ST2-deficient CD8+SL responses were restored by blockade of type I interferon signaling, suggesting that IL-33 balances IFN-I effects to control CD8+SL formation in chronic infection. IL-33 signals broadly augmented chromatin accessibility in CD8+SL and determined these cells' re-expansion potential.Our study identifies the IL-33-ST2 axis as an important CD8+SL-promoting pathway in the context of chronic viral infection.
Short Message Service Reminder Nudge for Parents and Influenza Vaccination Uptake in Children and Adolescents With Special Risk Medical Conditions
Authors: Jane Tuckerman, Kelly Harper, Thomas R. Sullivan, Alana R. Cuthbert, Jennifer Fereday, Jennifer Couper, Nicholas Smith, Andrew Tai, Andrew Kelly, Richard Couper, Mark Friswell, Louise Flood, Christopher C. Blyth, Margie Danchin, Helen S. Marshall
Journal: JAMA Pediatrics (2023)

Children with chronic medical conditions are at increased risk of severe influenza. Uptake of influenza vaccination in children and adolescents with these identified special risk medical conditions (SRMCs) is suboptimal.To assess the effectiveness of Flutext-4U, a parent short message service (SMS) reminder nudge intervention, in increasing influenza immunization in children and adolescents with SRMCs.This randomized clinical trial was conducted at a tertiary pediatric hospital in Adelaide, South Australia, from April 15 to September 30, 2021. Children and adolescents aged 6 months to younger than 18 years with SRMCs and a subspecialist outpatient appointment over a 5-month period during the Australian seasonal influenza vaccination season (April-August 2021) were eligible to participate. Follow-up was until September 30, 2021.Participants were randomly assigned (1:1 ratio) to control: clinician nudges (hospital vaccine availability, ease of access, and recommendation from hospital subspecialists) or SMS intervention (control conditions plus an additional SMS reminder nudge to parents), with randomization stratified by age group (<5 years, 5-14 years, or >14 to <18 years).The primary outcome was influenza vaccination, as confirmed by the Australian Immunisation Register.A total of 600 participants (intervention group: 298 [49.7%]; mean [SD] age, 11.5 [4.6] years; 162 female participants [54.4%]; control group: 302 [50.3%]; mean [SD] age, 11.4 [4.7] years; 155 female participants [51.3%]) were included. Influenza vaccination was 38.6% (113 of 293) in the SMS intervention group compared with 26.2% (79 of 302) in the control group (adjusted odds ratio [aOR], 1.79; 95% CI, 1.27-2.55; P = .001). Time to vaccine receipt was significantly lower among SMS participants (adjusted hazard ratio, 1.67; 95% CI, 1.25-2.22; P < .001). For participants randomly assigned by June 15, a significantly greater proportion receiving the SMS intervention were vaccinated during the optimal delivery period April to June 30 (SMS group: 40.0% [76 of 190] vs 25.4% [50 of 197]; aOR, 1.97; 95% CI, 1.28-3.06; P = .002).Results of this randomized clinical trial suggest that an additional SMS reminder nudge for parents delivered in the tertiary care hospital setting to children and adolescents with SMRCs resulted in higher influenza vaccine uptake compared with clinician nudges alone.ANZCTR Identifier: ACTRN12621000463875.
Omission of Author From Byline
Journal: JAMA Internal Medicine (2023)

Joseph A. Ladapo, MD, PhD; Stephanie L. Orstad, PhD; Soma Wali, MD; Judith Wylie-Rosett, EdD, RD; Chi-Hong Tseng, PhD; Un Young Rebecca Chung, BS; Miguel A. Cuevas, BS; Christina Hernandez, MPH; Susan Parraga, BS; Robert Ponce, BS; Victoria Sweat, MA; Sandra Wittleder, PhD; Andrew B. Wallach, MD; Suzanne B. Shu, PhD; Noah J. Goldstein, PhD; Isaac Dapkins, MD; Melanie Jay, MD
Antiretroviral therapy reveals triphasic decay of intact SIV genomes and persistence of ancestral variants
Authors: Emily J. Fray, Fengting Wu, Francesco R. Simonetti, Carolin Zitzmann, Narmada Sambaturu, Carmen Molina-Paris, Alexandra M. Bender, Po-Ting Liu, John D. Ventura, Roger W. Wiseman, David H. O’Connor, Romas Geleziunas, Thomas Leitner, Ruy M. Ribeiro, Alan S. Perelson, Dan H. Barouch, Janet D. Siliciano, Robert F. Siliciano
Journal: Cell Host & Microbe (2023)

The decay kinetics of HIV-1-infected cells are critical to understand virus persistence. We evaluated the frequency of simian immunodeficiency virus (SIV)-infected cells for 4 years of antiretroviral therapy (ART). The intact proviral DNA assay (IPDA) and an assay for hypermutated proviruses revealed short- and long-term infected cell dynamics in macaques starting ART ∼1 year after infection. Intact SIV genomes in circulating CD4+T cells showed triphasic decay with an initial phase slower than the decay of the plasma virus, a second phase faster than the second phase decay of intact HIV-1, and a stable third phase reached after 1.6–2.9 years. Hypermutated proviruses showed bi- or mono-phasic decay, reflecting different selective pressures. Viruses replicating at ART initiation had mutations conferring antibody escape. With time on ART, viruses with fewer mutations became more prominent, reflecting decay of variants replicating at ART initiation. Collectively, these findings confirm ART efficacy and indicate that cells enter the reservoir throughout untreated infection.
Health Status and Health Care Access Among Lesbian, Gay, and Bisexual Adults in the US, 2013 to 2018
Authors: Michael Liu, Sahil Sandhu, Sari L. Reisner, Gilbert Gonzales, Alex S. Keuroghlian
Journal: JAMA Internal Medicine (2023)

This cross-sectional study evaluated data from a large US survey (2013-2018) to determine how health status and access have changed among lesbian, gay, and bisexual adults compared with heterosexual counterparts.
Coronary Heart Disease Testing Before Kidney Transplant—A Call for Revised Guidance
Authors: Rohini V. Kopparam, Deborah Grady, Rita F. Redberg
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
AKT Blocks SIK1-Mediated Repression of STAT3 to Promote Breast Tumorigenesis
Authors: Zicheng Sun, Qiwei Jiang, Bing Gao, Xiaomei Zhang, Lang Bu, Lei Wang, Ying Lin, Wei Xie, Jie Li, Jianping Guo
Journal: Cancer Research (2023)

Abstract The PI3K–AKT signaling pathway is frequently dysregulated in cancer, and it is hyperactivated in approximately 50% of breast cancers. Although inhibitors directly targeting the PI3K–AKT axis have been developed, clinical efficacy has been limited to only a subset of patients. Identification of mechanisms underlying AKT-driven tumorigenesis could lead to alternative approaches to block pathway signaling and suppress breast tumor growth. Mass spectrometry–based analyses demonstrated that salt-inducible kinase 1 (SIK1) binds AKT and undergoes AKT-mediated phosphorylation, which compromises SIK1 tumor-suppressive functions. As a result, AKT relieved the binding and repression of STAT3 by SIK1 in a phosphorylation-dependent manner, resulting in breast cell tumorigenesis. Following AKT-mediated phosphorylation, SIK1 interacted with 14-3-3 and was translocated to the cytoplasm where the isomerase Pin1 facilitated SIK1 interaction with the E3 ligase ITCH to promote SIK1 ubiquitination and subsequent degradation. These findings indicate that SIK1 is a substrate of AKT that links AKT oncogenic function to STAT3 activation, highlighting targeting of the JAK2–STAT3 axis as a strategy to treat AKT-driven breast cancer. Significance: AKT binds and phosphorylates SIK1 to overcome SIK1-mediated repression of STAT3, indicating that STAT3 is a potential therapeutic target in breast cancer with hyperactive AKT signaling.
Cumulative 6-Year Risk of Screen-Detected Ductal Carcinoma In Situ by Screening Frequency
Authors: Brian L. Sprague, Shuai Chen, Diana L. Miglioretti, Charlotte C. Gard, Jeffrey A. Tice, Rebecca A. Hubbard, Erin J. Aiello Bowles, Peter A. Kaufman, Karla Kerlikowske
Journal: JAMA Network Open (2023)

Importance Detection of ductal carcinoma in situ (DCIS) by mammography screening is a controversial outcome with potential benefits and harms. The association of mammography screening interval and woman’s risk factors with the likelihood of DCIS detection after multiple screening rounds is poorly understood. Objective To develop a 6-year risk prediction model for screen-detected DCIS according to mammography screening interval and women’s risk factors. Design, Setting, and Participants This Breast Cancer Surveillance Consortium cohort study assessed women aged 40 to 74 years undergoing mammography screening (digital mammography or digital breast tomosynthesis) from January 1, 2005, to December 31, 2020, at breast imaging facilities within 6 geographically diverse registries of the consortium. Data were analyzed between February and June 2022. Exposures Screening interval (annual, biennial, or triennial), age, menopausal status, race and ethnicity, family history of breast cancer, benign breast biopsy history, breast density, body mass index, age at first birth, and false-positive mammography history. Main Outcomes and Measures Screen-detected DCIS defined as a DCIS diagnosis within 12 months after a positive screening mammography result, with no concurrent invasive disease. Results A total of 916 931 women (median [IQR] age at baseline, 54 [46-62] years; 12% Asian, 9% Black, 5% Hispanic/Latina, 69% White, 2% other or multiple races, and 4% missing) met the eligibility criteria, with 3757 screen-detected DCIS diagnoses. Screening round–specific risk estimates from multivariable logistic regression were well calibrated (expected-observed ratio, 1.00; 95% CI, 0.97-1.03) with a cross-validated area under the receiver operating characteristic curve of 0.639 (95% CI, 0.630-0.648). Cumulative 6-year risk of screen-detected DCIS estimated from screening round–specific risk estimates, accounting for competing risks of death and invasive cancer, varied widely by all included risk factors. Cumulative 6-year screen-detected DCIS risk increased with age and shorter screening interval. Among women aged 40 to 49 years, the mean 6-year screen-detected DCIS risk was 0.30% (IQR, 0.21%-0.37%) for annual screening, 0.21% (IQR, 0.14%-0.26%) for biennial screening, and 0.17% (IQR, 0.12%-0.22%) for triennial screening. Among women aged 70 to 74 years, the mean cumulative risks were 0.58% (IQR, 0.41%-0.69%) after 6 annual screens, 0.40% (IQR, 0.28%-0.48%) for 3 biennial screens, and 0.33% (IQR, 0.23%-0.39%) after 2 triennial screens. Conclusions and Relevance In this cohort study, 6-year screen-detected DCIS risk was higher with annual screening compared with biennial or triennial screening intervals. Estimates from the prediction model, along with risk estimates of other screening benefits and harms, could help inform policy makers’ discussions of screening strategies.
Poser
Authors: Bhuvana Chandra
Journal: Annals of Internal Medicine (2023)

Ad LibitumFebruary 2023PoserBhuvana Chandra, MDBhuvana Chandra, MDPorter Ranch, CaliforniaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M22-2163 Audio Reading - “Poser” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “Poser” by Bhuvana Chandra, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail A seizure is upon me, short-circuitingmy senses; I cannot hear the worldcalling, rent mute of responses. Wrenchedfrom my mooring with no tocsin's knell,I'm pitched into blackness, felledquick to the ground. Deaf now to myown sounds, undead but unalive, Mindin full outage, Will lacking guide.Aura relegated to a past all-forgotten;the present a vortex, in thrall to the fast,imperious dictates of my brain. Musclestauten, contract—unheeded by me.Nothing. The world is not missed. Forair-hungered flashes, “I” cease to exist.Control full-wrested; perceptions stilled—a puppet dependent on invisible strings.volts go awry. Brain commands body as... Author, Article, and Disclosure InformationAffiliations: Porter Ranch, CaliforniaCorresponding Author: Bhuvana Chandra, MD; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “Poser” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “Poser” by Bhuvana Chandra, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics Current IssueFebruary 2023Volume 176, Issue 2Page: 287 ePublished: 21 February 2023 Issue Published: February 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Effect of Adjunctive Simvastatin on Depressive Symptoms Among Adults With Treatment-Resistant Depression
Authors: M. Ishrat Husain, Imran B. Chaudhry, Ameer B. Khoso, Tayyeba Kiran, Nawaz Khan, Farooq Ahmad, John Hodsoll, M. Omair Husain, Haider A. Naqvi, Asad T. Nizami, Nasim Chaudhry, Hazrat A. Khan, Fareed Minhas, Jeffrey H. Meyer, Moin A. Ansari, Benoit H. Mulsant, Nusrat Husain, Allan H. Young
Journal: JAMA Network Open (2023)

Importance Immune-metabolic disturbances have been implicated in the pathophysiology of major depressive disorder and may be more prominent in individuals with treatment-resistant depression (TRD). Preliminary trials suggest that lipid-lowering agents, including statins, may be useful adjunctive treatments for major depressive disorder. However, no adequately powered clinical trials have assessed the antidepressant efficacy of these agents in TRD. Objective To assess the efficacy and tolerability of adjunctive simvastatin compared with placebo for reduction of depressive symptoms in TRD. Design, Setting, and Participants This 12-week, double-blind, placebo-controlled randomized clinical trial was conducted in 5 centers in Pakistan. The study involved adults (aged 18-75 years) with a Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) major depressive episode that had failed to respond to at least 2 adequate trials of antidepressants. Participants were enrolled between March 1, 2019, and February 28, 2021; statistical analysis was performed from February 1 to June 15, 2022, using mixed models. Intervention Participants were randomized to receive standard care plus 20 mg/d of simvastatin or placebo. Main Outcomes and Measures The primary outcome was the difference between the 2 groups in change in Montgomery-Åsberg Depression Rating Scale total scores at week 12. Secondary outcomes included changes in scores on the 24-item Hamilton Rating Scale for Depression, the Clinical Global Impression scale, and the 7-item Generalized Anxiety Disorder scale and change in body mass index from baseline to week 12. C-reactive protein and plasma lipids were measured at baseline and week 12. Results A total of 150 participants were randomized to simvastatin (n = 77; median [IQR] age, 40 [30-45] years; 43 [56%] female) or placebo (n = 73; median [IQR] age, 35 [31-41] years; 40 [55%] female). A significant baseline to end point reduction in Montgomery-Åsberg Depression Rating Scale total score was observed in both groups and did not differ significantly between groups (estimated mean difference for simvastatin vs placebo, −0.61; 95% CI, −3.69 to 2.46; P = .70). Similarly, there were no significant group differences in any of the secondary outcomes or evidence for differences in adverse effects between groups. A planned secondary analysis indicated that changes in plasma C-reactive protein and lipids from baseline to end point did not mediate response to simvastatin. Conclusions and Relevance In this randomized clinical trial, simvastatin provided no additional therapeutic benefit for depressive symptoms in TRD compared with standard care. Trial Registration ClinicalTrials.gov Identifier: NCT03435744
Ideation
Authors: Martin H. Ellbogen
Journal: Annals of Internal Medicine (2023)

Ad LibitumFebruary 2023IdeationMartin H. Ellbogen Jr., MDMartin H. Ellbogen Jr., MDNordland, WashingtonSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M22-0317 Audio Reading - “Ideation” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “Ideation” by Martin H. Ellbogen Jr., MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Who knows,Maybe a circuit reroutesOr a seal is broken,Neurons once bathed in monoamines and the likeAre deprived and unsettled,An inscrutable equilibrium altered.A window opens a crack, a cold mistPenetrates.A needling shivOpens an angry woundThat cannot be soothed,Only indulgedBy unease and doubt, by anguish,That whet its appetiteFor sleepTaunting itLeering at itShredding itUntil unbridled thoughts and notions and fearsBecome torrential rains andAll games end in ties and old lessons become rebukes and logic abandons reason ... Author, Article, and Disclosure InformationAuthors: Martin H. EllbogenJr., MDAffiliations: Nordland, WashingtonCorresponding Author: Martin H. Ellbogen Jr., MD; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “Ideation” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “Ideation” by Martin H. Ellbogen Jr., MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics February 2023Volume 176, Issue 2Page: 286 ePublished: 21 February 2023 Issue Published: February 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Psychometric Properties of Screening Instruments for Social Network Use Disorder in Children and Adolescents
Authors: Samantha Schlossarek, Hannah Schmidt, Anja Bischof, Gallus Bischof, Dominique Brandt, Stefan Borgwardt, Dillon T. Browne, Dimitri Christakis, Pamela Hurst-Della Pietra, Zsolt Demetrovics, Hans-Jürgen Rumpf
Journal: JAMA Pediatrics (2023)

Children and adolescents spend considerable time on the internet, which makes them a highly vulnerable group for the development of problematic usage patterns. A variety of screening methods have already been developed and validated for social network use disorder (SNUD); however, a systematic review of SNUD in younger age groups has not been performed.To review published reports on screening tools assessing SNUD in children and adolescents with a maximum mean age of 18.9 years.To identify instruments for the assessment of SNUD, a systematic literature search was conducted in the databases PsycINFO, PubMed, Web of Science, PsycArticles, and Scopus. The final search took place on May 2, 2022. Psychometric properties of available tools were examined and evaluated to derive recommendations for suitable instruments for individuals up to 18 years of age.A total of 5746 publications were identified, of which 2155 were excluded as duplicates. Of the remaining 3591 nonredundant publications, 3411 studies were assessed as not relevant after title and abstract screening. A full-text analysis of 180 remaining studies classified as potentially eligible resulted in a final inclusion of 29 studies revealing validation evidence for a total of 19 tools. The study quality was mostly moderate. With regard to validation frequency, 3 tools exhibited the largest evidence base: Social Media Disorder Scale (SMDS), the short version of the Bergen Facebook Addiction Scale, and Bergen Social Media Addiction Scale-Short Form (BSMAS-SF). Among these, 1 study tested a parental version (SMDS-P) for its psychometric properties. Taking all criteria into account, the strongest recommendation was made for the SMDS and BSMAS-SF.Results suggest that the SMDS-SF and BSMAS-SF were appropriate screening measures for SNUD. Advantages of the SMDS are the availability of a short version and the possibility of an external parental rating.